This invention provides a novel method for the treatment of gastrointestinal malignancies.
Patients with advanced unresectable colorectal carcinoma have a uniformly poor prognosis. In addition to the significant mortality from this disease, patients often experience severe morbidities including obstruction of the gastrointestinal tract, liver failure, massive ascites, cachexia and inanition.
The compound, 5-fluorouracil, is the principal chemotherapeutic agent which is employed against colorectal cancer even though it induces remissions in only 15-35% of patients with disseminated colorectal cancer. The patients who do respond rarely respond completely and the duration of the response is generally short. The median survival of treated patients is no better than that of untreated controls.
The failure of conventional chemotherapy to provide durable, disease--free remissions against gastrointestinal malignancies has prompted research aimed at developing alternative treatments which are more effective than 5-fluorouracil employed alone. One approach to enhancing the effect of 5-fluorouracil has been the concomitant use of agents which by themselves have little or no activity against refractory solid tumors, but which in combination modify the metabolism or disposition of 5-fluorouracil to amplify its anti-tumor activity.
The applicant has discovered that the use of 5-fluorouracil in a systematic dosage regimen with concomitant administration of interferon will provide a more effective chemotherapeutic approach to the treatment of gastrointestinal malignancies than the use of either drug alone. The applicant has confirmed the efficacy of the novel method of the invention by studies in human cancer cell lines and in clinical experiments. These results are surprising and unexpected in view of the lack of prior success with combinations of 5-fluorouracil and interferon which were probably due to the use of an inadequate dosage and offers the first demonstration of the enhancement by interferon of the activity of any chemotherapeutic agent against a refractory solid tumor.